Associations Of Persistent Organic Pollutants Research Articles

Environmental Exposure to Persistent Organic Pollutants and Its Association with Endometriosis Risk: Implications in the Epithelial-Mesenchymal Transition Process.

We aimed to explore the relationship of adipose tissue concentrations of some persistent organic pollutants (POPs) with the risk of endometriosis and the endometriotic tissue expression profile of genes related to the endometriosis-related epithelial-mesenchymal transition (EMT) process. This case-control study enrolled 109 women (34 cases and 75 controls) between January 2018 and March 2020. Adipose tissue samples and endometriotic tissues were intraoperatively collected to determine concentrations of nine POPs and the gene expression profiles of 36 EMT-related genes, respectively. Associations of POPs with endometriosis risk were explored with multivariate logistic regression, while the relationship between exposure and gene expression profiles was assessed through Spearman correlation or Mann-Whitney U tests. After adjustment, increased endometriosis risk was associated with p,p'-DDT, PCB-180, and ΣPCBs. POP exposure was also associated with reduced gene expression levels of the CLDN7 epithelial marker and increased levels of the ITGB2 mesenchymal marker and a variety of EMT promoters (HMGA1, HOXA10, FOXM1, DKK1, CCR1, TNFRSF1B, RRM2, ANG, ANGPT1, and ESR1). Our findings indicate that exposure to POPs may increase the risk of endometriosis and might have a role in the endometriosis-related EMT development, contributing to the disease onset and progression. Further studies are warranted to corroborate these findings.

Gender- and Age-Group Specific Association of Persistent Organic Pollutants (POPs) Exposure with Diabetes Mellitus: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

Exposure to persistent organic pollutants (POPs) has been reported as a potential risk factor for diabetes in adults. However, effect modifications by sex and age, especially among Asian populations, have seldom been investigated. In the present study, we assessed associations of major POPs exposure including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), with diabetes in Korean adults (n = 1,295), a subset of the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (2015-2017). In the adult population, serum levels of dichlorodiphenyltrichloroethanes (DDTs) and PCB167 showed an increased odds ratio (OR) for diabetes. When stratified by gender, associations became stronger and more consistent in women: In women, serum levels of OCPs including p,p'-DDT, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and ΣOCPs and mono-ortho PCBs, such as PCB118 and PCB157, were significantly associated with diabetes. In the male participants, however, no significant positive associations were detected. When stratified by a cutoff age of 50 years, most studied POPs except PBDEs, i.e., p,p'-DDT, p,p'-DDE, PCB118, PCB157, PCB167, PCB138, and PCB153, showed significant associations with diabetes, in the older adults. In the younger group, however, no measured POPs showed a significant positive association. Effects of endogenous sex hormones or interaction of POPs on aryl hydrocarbon receptors may partly explain the observed differences by gender and age, although further experimental confirmations should follow. Our findings show that POPs exposure at the current levels is associated with diabetes among general Korean adults, and such associations could be modified by gender and age.

Associations of persistent organic pollutants (POPs) with diabetes in women from the Hispanic Community Health Study/ Study of Latinos (HCHS/SOL)

Associations of persistent organic pollutants (POPs) with diabetes in women from the Hispanic Community Health Study/ Study of Latinos (HCHS/SOL)

Cross-sectional associations of persistent organic pollutants measured in adipose tissue and metabolic syndrome in clinically diagnosed middle-aged adults

IntroductionAlthough often overlooked in clinical settings, accumulation of persistent organic pollutants (POPs) in visceral adipose tissue (VAT) is thought to be a relevant risk factor for metabolic syndrome (MetS). MethodsOne hundred and seventeen patients undergoing non-oncological surgery were randomly recruited and classified as MetS + if presented 3 out of the 5 MetS components: waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP, respectively), serum glucose, insulin, triglycerides (TG) and high-density lipoprotein (HDL) cholesterol levels, according International Diabetes Federation (IDF) criteria. Seventeen organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in adipose tissue samples. Linear, logistic and weighted quantile sum (WQS) regression models, adjusted for age and sex, were performed. ResultsOne third of the participants were males (36.8%) with a median age of 44 years, showing clinical evidences of MetS (35.0%). Adjusted linear regression models showed that WC correlated positively with all OCP concentrations. Higher fasting serum glucose levels were related to higher HCB and γ-HCH concentrations. The remaining OCPs and PCBs were not associated with this MetS component. HCB was inversely associated with HDL cholesterol levels, while PCB-180 was positively associated. HCB and γ-HCH concentrations were also positively correlated with DBP and SBP levels. PCB-138 was also positively associated with SBP. Adjusted logistic models revealed that exposure to HCB and γ-HCH were associated with increased odds of MetS [ORs (95%CI) 1.53 (1.22–1.92) and 1.39 (1.10–1.76) respectively; p < 0.01]. No associations were observed for the remaining POPs. WQS models showed a positive and significant mixture effect of POPs on the odds of MetS (exp [beta] = 2.34; p < 0.001), with γ-HCH (52.9%), o,p'-DDT (26.9%) and HCB (19.7%) driving the association. ConclusionsOur findings support that POPs accumulated in VAT, specifically HCB and (gamma)-HCH, are associated with both isolated components and clinically diagnosed SMT.

Sex, menopause, and age differences in the associations of persistent organic pollutants with thyroid hormones, thyroxine-binding globulin, and peripheral deiodinase activity: A cross-sectional study of the general Korean adult population

Persistent organic pollutants (POPs) can disrupt the thyroid hormone system in humans. We assessed the associations of several POPs with serum thyroid hormones (T3 and T4) and thyroid-stimulating hormone, and investigated the modulating effects of sex, menopausal status, and age on these associations, in a subgroup of the adult population (n = 1250) from the Korean National Environmental Health Survey. PCB105 and PCB118 were negatively associated with total T4 in premenopausal females and males aged <50, whereas the associations were insignificant in other groups. PCB180, p,p′-DDE, and p,p′-DDT showed positive associations with total T3 in postmenopausal females; however, among males aged ≥50, PCB118, PCB138, and p,p′-DDE showed negative associations with total T3. The effects of exposure to multiple POPs were examined in multi-factor analyses. Factor 2 comprised PCB52, hexachlorobenzene, and BDE-47 was associated with an increase in free T4 in premenopausal females (β = 0.015, p = 0.024), while Factor 1, which contained most POPs, was associated with a change in total T3 in postmenopausal females (β = 0.032, p = 0.040) and males aged ≥50 (β = −0.039, p = 0.023). Changes in total T4 or total T3 could be explained by differences in thyroxine-binding globulin (TBG) and peripheral deiodinase activity (GD). Negative associations of TBG with PCB105 in premenopausal females and PCB153 in males aged <50 may mediate the effect of decreasing total T4. PCB180, p,p′-DDE, p,p′-DDT, and Factor 1 were positively associated with GD, which is consistent with an increased total T3 in postmenopausal females. PCB118 was negatively associated with GD and total T3 in males aged ≥50. BDE-47 and β-hexachlorocyclohexane were associated with thyroid autoantibodies in premenopausal females and males aged <50. Our observations suggest that the thyroid-disrupting effects of POPs may differ by sex, sex hormonal status, and age, and may be mediated by TBG and GD.

Association of persistent organic pollutants with sensorimotor neuropathy in participants with and without diabetes or prediabetes: Results from the population-based KORA FF4 study.

Concentrations of persistent organic pollutants (POPs) have been associated with an increased type 2 diabetes (T2D) risk. It remains unclear whether POPs are also associated with the risk of diabetes complications including neuropathy and evidence on this topic is scarce. We aimed to investigate the hypothesis that low-dose background concentrations of POPs were positively associated with distal sensorimotor polyneuropathy (DSPN). This cross-sectional study was based on data from the second follow-up (FF4, 2013-2014, N=2279) of the population-based KORA S4 study (Augsburg, Germany). The study sample consisted of 200 participants, including four groups of 50 persons each with known T2D, prediabetes, newly diagnosed diabetes, and normal glucose tolerance (NGT) based on an oral glucose tolerance test. We analyzed the association of six most abundant serum concentrations of POPs, including polychlorinated biphenyls (PCBs) as well as organochlorine (OC) pesticides, with DSPN by multivariable logistic regression adjusted for age, sex, glycaemic status, body mass index, physical activity, smoking and alcohol consumption. We assessed effect modification by age, sex, glycaemic status and obesity and conducted two-pollutant models to check the robustness of the estimates. For all pollutants, the main models indicated no significant association of having DSPN but pointed to rather decreased odds for DSPN. Two-pollutant models supported these findings, though only the association between the combination of PCB-138 and beta-hexachlorocyclohexane (β-HCH) (OR: 0.59; 95% CI: 0.35-0.99) with DSPN became significant. No effect modification was found by age, sex, glycaemic status and obesity. Low-dose concentrations of POPs were not associated with increased odds of having DSPN in T2D, prediabetes and NGT.

Associations of persistent organic pollutants in human adipose tissue with retinoid levels and their relevance to the redox microenvironment

Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment. Retinol was measured in both serum and adipose tissue along with RBP4 levels in serum samples of 236 participants of the GraMo adult cohort. Associations were explored by multivariable linear regression analyses and Weighted Quantile Sum regression. Polychlorinated biphenyls (PCBs) 180, 153 and 138 were related to decreased adipose tissue retinol levels and increased serum RBP4/retinol ratio. Dicofol concentrations > limit of detection were associated with decreased retinol levels in serum and adipose tissue. Additionally, increased adipose tissue retinol levels were linked to an attenuation in previously-reported associations of adipose tissue PCB-153 with in situ superoxide dismutase activity. Our results revealed a suggestive link between retinoids, PCBs and redox microenvironment, potentially relevant for both mechanistic and public health purposes.

Associations of PCBS, dioxins and furans with follicle-stimulating hormone and luteinizing hormone in postmenopausal women: National Health and Nutrition Examination Survey 1999–2002

BackgroundThe general population is exposed to the group of endocrine disrupting chemicals persistent organic pollutants (POPs), that includes polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). ObjectivesThe aim of this research was to evaluate the associations of serum levels of PCB, PCDD, and PCDF congeners with follicle stimulating hormone (FSH) and luteinizing hormone (LH) in postmenopausal women not taking exogenous hormones. We hypothesized that associations of POPs with these gonadotropins could be modified by factors affecting endogenous hormones. MethodsCross-sectional analyses were conducted on data from 89 postmenopausal women using data from the National Health and Nutrition Examination Survey (NHANES). POPs were summarized based on classification schemes thought to reflect toxicological properties. Associations of POPs and gonadotropin hormones were modeled with multivariable regression models. When evidence of interaction was found, conditional effects were estimated. ResultsWe found inverse associations of LH, but not FSH, with exposure to anti-estrogenic and/or dioxin-like POPs, but not with non dioxin-like PCBs. A doubling of dioxin-like toxic equivalents (TEQs) was associated with a decrease in LH of 11.9% (95% CI = −21.3%, −1.4%, p = 0.03). Inverse associations were enhanced by potential effect modifiers related to both direct and indirect estrogenicity, including obesity and the obesity-related condition inflammation. ConclusionsThese investigations support a pattern of endocrine-disrupting effects by dioxin-like POPs among postmenopausal women, especially those with conditions related to peripheral estrogenicity.

Can persistent organic pollutants distinguish between two opposite metabolic phenotypes in lean Koreans?

AimsThis study investigated the association of persistent organic pollutants (POPs), an emerging new risk factor for type 2 diabetes and the metabolic syndrome, with the presence of opposite phenotypes of glucose and lipid metabolism among normal-weight Koreans of similar body composition. MethodsFifty subjects, randomly selected from an ongoing community-based cohort study, from two opposite phenotype groups — metabolically unhealthy normal weight (MUHNW) and metabolically healthy normal weight (MHNW) — were matched for waist circumference, visceral fat mass and demographic variables, then compared for serum concentrations of POPs. ResultsMost POPs (10 out of 13 compounds) were present in higher serum concentrations in the MUHNW than in the MHNW. In particular, serum concentrations of all compounds of the organochlorine pesticide class were 2.2 to 4.7 times higher in cases than in controls. Compared with the lowest tertile of summary measures of POPs, Odds ratios (95% confidence interval) for the second and third tertiles were 7.4 (1.9–29.4) and 10.4 (2.6–41.2), respectively. Adjusting for possible confounders did not change the results. ConclusionTaken altogether, these findings from the present and previous studies suggest that increased serum POP concentrations may play an important role in the development of unhealthy metabolic phenotypes in lean people.

Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends=0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends=0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend=0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends=0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend=0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis.

Persistent Organic Pollutants and Concern Over the Link with Insulin Resistance Related Metabolic Diseases.

Persistent organic pollutants (POPs) are mostly halogenated compounds tending to persist in the environment, enter into the food chain, and accumulate in fat mass of mammals due to their high lipophilicity. They include some organochlorine pesticides, polychlorinated biphenyls, brominated flame retardants and polycyclic aromatic hydrocarbons. Some of these chemicals were widely used in the past so that their residues can be detected in the human body, though their usage has been banned for years. POPs have been shown to perturb the health of biological systems in different ways evidenced by carcinogenicity and disrupting effects on endocrine, immune, and reproductive systems. There are many epidemiologic and experimental studies on the association of exposure to POPs with insulin resistance and related metabolic disorders like obesity, diabetes, and metabolic syndrome. Inflammation as a known mechanism accompanying insulin resistance has also been shown to arise in insulin target tissues exposed to POPs. This review addresses the breast milk concentration of POPs in different regions of the world, synthesizes the current information on the association of POPs with insulin resistance related metabolic disorders, and discusses the inflammation as an involved mechanism. Considering high prevalence of insulin resistance related metabolic diseases and their relation with POPs, much need is felt regarding international and regional programs to not only limit their production and usage but eliminate these persistent pollutants from the environment.

한국 성인의 혈청 잔류성 유기오염물질 농도와 연령 및 체질량지수와의 관련성

Objectives: Persistent organic pollutants (POPs) are known to be the detrimental chemicals in the body, even at low levels, and are stored in adipose tissue. Recently, POPs have been reported to be associated with chronic diseases, including cancer and cardiovascular disease, and aging and obesity are reported as common factors in chronic disease. However, there have been only a few studies on the associations of POPs with age and body mass index (BMI) in Korea. Therefore, we analyzed the associations of serum POPs levels with age and BMI in Korea. Methods: This cross-sectional study includes 444 subjects (253 men and 191 women) from the Korean Cancer Prevention Study-II (2004-2011). Serum levels of 33 polychlorinated biphenyls (PCBs) and 19 organochlorine pesticides (OCPs) were measured by a gas chromatographer (Agilent 6890) coupled to high resolution mass spectrometer (JEOL JMS-800D). Results: Concentrations of PCB 153 (men: 12.26 ng/g lipid, women: 10.50 ng/g lipid) and p,p`-DDE (men: 94.66 ng/g lipid, women: 96.66 ng/g lipid) were the highest among serum PCBs and OCPs, respectively. PCBs and OCPs were significantly positively correlated with age in both sexes. After adjustment for age, non-dioxin like PCBs were significantly negatively correlated with body mass in women. However, cis-heptachlor epoxide was significantly positively correlated with body mass index in both sexes. When analyzed by sex, stronger associations were shown between POPs and age in men and POPs and BMI in women. Conclusion: These results may provide baseline data for the study of POPs and for the health management field in Korea.

Effects of age, sex, and persistent organic pollutants on DNA methylation in children

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies have examined the effects of host factors on LINE-1 and Alu methylation in children. We characterized the relationship of age, sex, and prenatal exposure to persistent organic pollutants (POPs), dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs), with DNA methylation in a birth cohort of Mexican-American children participating in the CHAMACOS study. We measured Alu and LINE-1 methylation by pyrosequencing bisulfite-treated DNA isolated from whole blood samples collected from newborns and nine-year old children (n = 358). POPs were measured in maternal serum during late pregnancy. Levels of DNA methylation were lower in nine-year olds compared to newborns and were higher in boys compared to girls. Higher prenatal DDT/E exposure was associated with lower Alu methylation at birth, particularly after adjusting for cell type composition (P = 0.02 for o,p' -DDT). Associations of POPs with LINE-1 methylation were only identified after examining the co-exposure of DDT/E with PBDEs simultaneously. Our data suggest that repeat element methylation can be an informative marker of epigenetic differences by age and sex and that prenatal exposure to POPs may be linked to hypomethylation in fetal blood. Accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies.

Evaluation of the Association between Persistent Organic Pollutants (POPs) and Diabetes in Epidemiological Studies: A National Toxicology Program Workshop Review

Background: Diabetes is a major threat to public health in the United States and worldwide. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health.Objective: We assessed the epidemiologic literature for evidence of associations between persistent organic pollutants (POPs) and type 2 diabetes.Methods: Using a PubMed search and reference lists from relevant studies or review articles, we identified 72 epidemiological studies that investigated associations of persistent organic pollutants (POPs) with diabetes. We evaluated these studies for consistency, strengths and weaknesses of study design (including power and statistical methods), clinical diagnosis, exposure assessment, study population characteristics, and identification of data gaps and areas for future research.Conclusions: Heterogeneity of the studies precluded conducting a meta-analysis, but the overall evidence is sufficient for a positive association of some organochlorine POPs with type 2 diabetes. Collectively, these data are not sufficient to establish causality. Initial data mining revealed that the strongest positive correlation of diabetes with POPs occurred with organochlorine compounds, such as trans-nonachlor, dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like chemicals. There is less indication of an association between other nonorganochlorine POPs, such as perfluoroalkyl acids and brominated compounds, and type 2 diabetes. Experimental data are needed to confirm the causality of these POPs, which will shed new light on the pathogenesis of diabetes. This new information should be considered by governmental bodies involved in the regulation of environmental contaminants.

Associations of persistent organic pollutants with abdominal obesity in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

ObjectivesIn animal experiments, persistent organic pollutants (POPs) have induced visceral obesity. To address this possibility in humans, we evaluated associations between POPs and abdominal obesity both cross-sectionally and prospectively. MethodsTwenty-one plasma POPs (16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured at baseline in 970 participants aged 70years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), with prospective analyses in 511 participants re-examined after 5years. Abdominal obesity was defined by an increased waist circumference. ResultsIn the cross-sectional analyses, concentrations of the less chlorinated PCBs, OC pesticides such as p,p′-DDE and dioxin had adjusted odds ratios of 2 to 3 for abdominal obesity. Many relations had inverted U-shapes rather than being linear, particularly in women. In contrast, concentrations of highly chlorinated PCBs were strongly inversely associated with abdominal obesity. In a single model including summary measures of the less chlorinated PCBs, highly chlorinated PCBs, and OC pesticides, both the positive associations and inverse associations strengthened. Similar but somewhat weaker associations were seen between POPs and risk of development of abdominal obesity in the prospective analyses. ConclusionUsing both a cross-sectional and a prospective design, low-dose exposure to less chlorinated PCBs, p,p′-DDE, and dioxin, were associated with existence or development of abdominal obesity, while highly chlorinated PCBs had an opposite association in an elderly population, despite the previous observation of higher incident diabetes associated with these same PCBs.

Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers

BackgroundStudies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking.ObjectivesThis study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers.MethodsThe cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status.ResultsDDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status.ConclusionsThis study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.